What is the recommended treatment and dosage for insomnia using Belsomra (suvorexant)?

Belsomra (Suvorexant) for Insomnia Treatment

Recommended Dosing

Start with 10 mg taken once nightly within 30 minutes of bedtime (with at least 7 hours remaining before planned awakening), and increase to a maximum of 20 mg if the 10 mg dose is well-tolerated but ineffective. 1

• The FDA-approved starting dose is 10 mg, which can be titrated up to a maximum of 20 mg based on response and tolerability 1
• Take no more than once per night, and avoid taking with or soon after meals as this delays the time to effect 1
• The minimum effective dose should always be used to minimize exposure-related adverse effects 1

Clinical Indication and Evidence Base

Suvorexant is indicated specifically for sleep maintenance insomnia, with weaker evidence for sleep onset difficulties. 2

• The American Academy of Sleep Medicine provides a WEAK recommendation for suvorexant as treatment for sleep maintenance insomnia in adults 2
• Objective polysomnography data show clinically significant reductions in wake after sleep onset (16-28 minutes greater than placebo) 2
• Total sleep time improvement was modest (only 10 minutes longer than placebo), which barely reaches clinical significance 2
• Sleep onset improvement at standard doses (10 mg, 15/20 mg) failed to meet clinical significance, though 20 mg doses showed better effects 2

Special Population Dosing Adjustments

Obese women require particular caution due to significantly increased drug exposure and should generally remain at lower doses. 1

• Exposure is increased in obese patients compared to non-obese patients, and in women compared to men 1
• For obese women specifically, carefully consider the increased risk of exposure-related adverse effects before dose escalation 1

Drug Interaction Dosing

When combined with moderate CYP3A inhibitors, reduce the dose to 5 mg (maximum 10 mg); avoid use entirely with strong CYP3A inhibitors. 1

• Moderate CYP3A inhibitors: Start at 5 mg, generally do not exceed 10 mg 1
• Strong CYP3A inhibitors: Suvorexant is not recommended for concurrent use 1
• When combined with other CNS depressants, consider dosage reduction of suvorexant and/or the other drug due to additive effects 1

Place in Therapy Algorithm

Suvorexant is a second-line pharmacological option, reserved for patients who have failed or cannot tolerate first-line agents like eszopiclone, zolpidem, or temazepam. 2, 3

• The American Academy of Sleep Medicine recommends eszopiclone (2-3 mg), zolpidem (10 mg), or temazepam (15-30 mg) as preferred agents for sleep maintenance insomnia 3
• Suvorexant's modest efficacy (only 10 minutes improvement in total sleep time) and weak recommendation grade place it behind these alternatives 2
• Consider suvorexant when patients have contraindications to benzodiazepine receptor agonists or prefer a non-GABA mechanism 2

Critical Safety Warnings

Next-day driving impairment is a significant concern, particularly at the 20 mg dose, and patients must be counseled about this risk. 1

• CNS depressant effects can persist for several days after discontinuation 1
• A driving study in healthy adults demonstrated impaired driving ability in some individuals taking 20 mg 1
• Patients on 20 mg should be cautioned against next-day driving and activities requiring full mental alertness 1
• Even at lower doses, individual variation in sensitivity exists, so all patients require counseling about potential driving impairment 1
• Discontinue or decrease the dose if daytime somnolence develops 1

Common Adverse Effects

Somnolence is the most common adverse effect, occurring at rates requiring treatment of 13 patients to cause one additional case of somnolence (NNH = 13 for higher doses). 4

• Most common adverse effects (≥5% and twice placebo rate): somnolence 1, 4
• Other frequent effects include fatigue, abnormal dreams, headache, dizziness, and upper respiratory tract infection 5, 6
• Number needed to harm for somnolence: 13 (95% CI 11-18) for 40/30 mg doses, and 28 (95% CI 17-82) for 20/15 mg doses 4
• Rare but serious concerns include sleep walking, nighttime behaviors, muscle weakness, and suicidal ideation 7

Contraindications

Suvorexant is absolutely contraindicated in patients with narcolepsy. 1

Advantages Over Alternatives

Unlike benzodiazepines and Z-drugs, suvorexant shows no evidence of rebound insomnia or withdrawal effects after 3-12 months of nightly use. 4

• No rebound insomnia observed upon discontinuation after chronic use 4
• No withdrawal effects documented in clinical trials 4
• Different mechanism of action (orexin receptor antagonist) compared to GABA-ergic agents may offer advantages in specific patient populations 8

Efficacy Benchmarks

Number needed to treat for clinical response (≥6 point improvement on Insomnia Severity Index at 3 months) is 8 for both higher and lower dose regimens. 4

• NNT vs. placebo: 8 (95% CI 6-14) for both dose regimens 4
• Efficacy and tolerability profiles are similar for patients <65 and ≥65 years of age 4
• Subjective improvements in sleep quality and total sleep time are more pronounced than objective polysomnography measures 5